Petrović, Voin and Petrović, Sandra and Joksi, Gordana and Savić, Jasmina and Čolović, Mirjana and Cinellu, Maria Agostina and Massai, Laura and Messori, Luigi and Vasić, Vesna (2014) Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes. Journal of Inorganic Biochemistry, Vol. 140 , p. 228-235. ISSN 0162-0134. eISSN 1873-3344. Article.
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Na+/K+-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy source to drive excess Na+ ions out of the cell in exchange for K+ ions. We explored whether three representative cytotoxic gold(III) compounds might interfere with Na+/K+-ATPase and cause its inhibition at pharmacologically relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy = 2,2′-bipyridine), [Au(pydmb-H)(CH3COO)2] (pydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipydmb-H)(OH)][PF6] (bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na+/K+-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na+/K+-ATPase inhibition. It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes.
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